Gonadotropin-releasing hormone agonists reduce the migratory and the invasive behavior of androgen-independent prostate cancer cells by interfering with the activity of IGF-I

  • Authors:
    • Marina Montagnani Marelli
    • Roberta M. Moretti
    • Stefania Mai
    • Patrizia Procacci
    • Patrizia Limonta
  • View Affiliations

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijo.30.1.261
  • Pages: 261-271
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Abstract

Androgen-independent prostate carcinoma is characterized by a high proliferation rate and by a strong metastatic behavior. We have previously shown that GnRH agonists exert a direct and specific inhibitory action on the proliferation of androgen-independent prostate cancer cells (DU 145). These compounds mainly act by interfering with the mitogenic activity of growth factors, such as the insulin-like growth factor-I (IGF-I). The present experiments were performed to clarify whether GnRH agonists might also affect the migratory and the invasive behavior of androgen-independent prostate cancer cells and to define their mechanism of action. First we showed that the GnRH agonist Leuprolide reduces the migration of DU 145 cells towards a chemoattractant and their ability to invade a reconstituted basement membrane. Experiments were then performed to clarify whether the GnRH agonist might act by interfering with the pro-metastatic activity of IGF-I. We found that, in androgen-independent prostate cancer cells, Leuprolide: a) interferes with the IGF-I system (receptor protein expression and tyrosine-phosphorylation); b) abrogates the IGF-I-induced phosphorylation of Akt (a kinase previously shown by us to mediate the pro-metastatic activity of IGF-I in prostate cancer cells); c) counteracts the migration and the invasive activity of the cells stimulated by IGF-I; d) abolishes the effects of IGF-I on cell morphology, on actin cytoskeleton organization and on αvβ3 integrin expression/cellular localization. These data indicate that GnRH agonists, in addition to their well known antiproliferative effect, can also exert a significant inhibitory activity on the migratory and invasive behavior of androgen-independent prostate cancer cells, expressing the GnRH receptor. GnRH agonists act by interfering with the pro-metastatic activity of the growth factor IGF-I.

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January 2007
Volume 30 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Montagnani Marelli M, Moretti RM, Mai S, Procacci P and Limonta P: Gonadotropin-releasing hormone agonists reduce the migratory and the invasive behavior of androgen-independent prostate cancer cells by interfering with the activity of IGF-I. Int J Oncol 30: 261-271, 2007.
APA
Montagnani Marelli, M., Moretti, R.M., Mai, S., Procacci, P., & Limonta, P. (2007). Gonadotropin-releasing hormone agonists reduce the migratory and the invasive behavior of androgen-independent prostate cancer cells by interfering with the activity of IGF-I. International Journal of Oncology, 30, 261-271. https://doi.org/10.3892/ijo.30.1.261
MLA
Montagnani Marelli, M., Moretti, R. M., Mai, S., Procacci, P., Limonta, P."Gonadotropin-releasing hormone agonists reduce the migratory and the invasive behavior of androgen-independent prostate cancer cells by interfering with the activity of IGF-I". International Journal of Oncology 30.1 (2007): 261-271.
Chicago
Montagnani Marelli, M., Moretti, R. M., Mai, S., Procacci, P., Limonta, P."Gonadotropin-releasing hormone agonists reduce the migratory and the invasive behavior of androgen-independent prostate cancer cells by interfering with the activity of IGF-I". International Journal of Oncology 30, no. 1 (2007): 261-271. https://doi.org/10.3892/ijo.30.1.261